Key result
Trastuzumab-induced cardiotoxicity in breast cancer survivors was associated with lower long-term LVEF (56.9% vs 62.4%; P<0.001) and peak oxygen consumption (22.9 vs 27.0 mL/kg/min; P=0.03).
Why the study?
Little was known regarding the long-term effects of treatment-induced cardiotoxicity on cardiopulmonary function in survivors of trastuzumab-treated ERBB2-positive breast cancer.
Is a history of trastuzumab-induced cardiotoxicity associated with long-term cardiopulmonary dysfunction in survivors of ERBB2-positive breast cancer?
Cross-Sectional (n=57)
No
Is a history of trastuzumab-induced cardiotoxicity associated with long-term cardiopulmonary dysfunction in survivors of ERBB2-positive breast cancer?
Trastuzumab-induced cardiotoxicity in breast cancer survivors is associated with long-term subclinical cardiopulmonary impairment, including reduced peak VO2 and global longitudinal strain, even years after treatment completion.
Answers are grounded in this paper and cite their sources.
Lower LVEF after cardiotoxicity may warrant surveillance; cross-sectional data leaves open causality and outcome impact.
Importance: Trastuzumab improves outcomes in patients with ERBB2-positive (formerly HER2) breast cancer but is associated with treatment-induced cardiotoxicity, most commonly manifest by an asymptomatic decline in left ventricular ejection fraction (LVEF). Little is known to date regarding the long-term effects of treatment-induced cardiotoxicity on cardiopulmonary function in patients who survive trastuzumab-treated breast cancer. Objective: To determine whether treatment-induced cardiotoxicity recovers or is associated with long-term cardiopulmonary dysfunction in survivors of ERBB2-positive breast cancer. Design, Setting, and Participants: This cross-sectional case-control study enrolled patients with nonmetastatic ERBB2-positive breast cancer after completion of trastuzumab-based therapy (median, 7.0 [interquartile range (IQR), 6.2-8.7] years after therapy) who met 1 of 2 criteria: (1) cardiotoxicity (TOX group) developed during trastuzumab treatment (ie, asymptomatic decrease of LVEF≥10% from baseline to <55% [n = 22]) or (2) no evidence of cardiotoxicity during trastuzumab treatment (NOTOX group [n = 20]). Patients were treated at the Memorial Sloan Kettering Cancer Center. Fifteen healthy control participants (HC group) were also enrolled for comparison purposes. All groups were frequency matched by age strata (<55, 55-64, and ≥65 years). Data were collected from September 9, 2016, to August 10, 2018, and analyzed from November 20, 2018, to August 12, 2019. Main Outcomes and Measures: Speckle-tracking echocardiography and maximal cardiopulmonary exercise testing were performed to measure indices of left ventricular function (including LVEF and global longitudinal strain [GLS]) and peak oxygen consumption (peak VO2). Results: A total of 57 participants (median age, 60.8 [IQR, 52.7-65.7] years) were included in the analysis. Overall, 38 of 42 patients with breast cancer (90%) were treated with anthracyclines before trastuzumab. Resting mean (SD) LVEF was significantly lower in the TOX group (56.9% [5.2%]) compared with the NOTOX (62.4% [4.0%]) and HC (65.3% [2.9%]) groups; similar results were found for GLS (TOX group, -17.8% [2.2%]; NOTOX group, -19.8% [2.2%]; HC group, -21.3% [1.8%]) (P < .001). Mean peak VO2 in the TOX group (22.9 [4.4] mL/kg/min) was 15% lower compared with the NOTOX group (27.0 [5.3] mL/kg/min; P = .03) and 25% lower compared with the HC group (30.5 [3.4] mL/ kg/min; P < .001). In patients with breast cancer, GLS was significantly associated with peak VO2 (β coefficient, -0.75; 95% CI, -1.32 to -0.18). Conclusions and Relevance: Treatment-induced cardiotoxicity appears to be associated with long-term marked impairment of cardiopulmonary function and may contribute to increased risk of late-occurring cardiovascular disease in survivors of ERBB2-positive breast cancer.
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Yu et al. (2020) conducted a cross-sectional in ERBB2-positive breast cancer (n=57). Treatment-induced cardiotoxicity vs. No cardiotoxicity and healthy controls was evaluated on Left ventricular ejection fraction (LVEF) (p=<0.001). Trastuzumab-induced cardiotoxicity in breast cancer survivors was associated with lower long-term LVEF (56.9% vs 62.4%; P<0.001) and peak oxygen consumption (22.9 vs 27.0 mL/kg/min; P=0.03).
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